1. Field of the Invention
This invention relates to a process for the separation of biotechnologically produced valuable materials from a cell suspension by crossflow microfiltration using porous polymeric tubes with micropores &gt;0.1 .mu.m as membranes through which the fermenter solution flows at a rate of &gt;2 m/s, a pressure difference of less than 5 bar prevailing between the concentrate side and the permeate side.
2. Description of Related Art
A fairly recent development in the field of solid/liquid separation is crossflow microfiltration ("Development Studies of Crossflow Microfiltration", R. Bertera, H. Steven, M. Metcalfe, The Chemical Engineer, June 1984, pp. 10 et seq).
One of the potential applications of this membrane microfiltration technique is in the separation of extracellular valuable materials, particularly those of relatively high molecular weight, from cell bodies and other solids.
This separation in culture and nutrient solutions such as for example fermenter solutions, of dissolved extracellular valuable materials from cells, cell fragments and other solids emanating from the nutrient medium is extremely problematical on account of the microsize of the solids and bacterial cell to be retained which vary from 0.2 to 5 .mu.m in size, the small difference in density between the fermenter solution and the solids and bacterial cells to be separated off, the compressibility of the solids and bacterial cells and the frequently non-Newtonian flow behavior of the relatively high viscosity fermenter solutions.
Accordingly, conventional solid/liquid separation techniques and equipment, such as filtration and centrifuging using, for example, high-performance separators or filtration units, are still being used in industry although they are at the limit of economy and perform very inefficiently in this field of biotechnology.
At the present time, very few technical applications going beyond the laboratory scale, for example the thickening of suspension or the separation of emulsions, are known for the technique of crossflow microfiltration suitable for the separation of dissolved substances of relatively high molecular weight.
The industrial application of crossflow microfiltration for the separation or rather isolation of extracellular materials of relatively high molecular weight from culture or fermenter solutions, such as for example the isolation of alkaline protease for the recovery of enzymes, is attended by the difficulties described above. However, the main problem involved in the commercial operation of the crossflow microfiltration technique in this biotechnical application is the surface layer forming on the surface of the membrane which, in view of the concentration polarization, prevents the passage of the valuable materials through the membrane and hence causes retention (holding back of the valuable materials) and limits the flow of permeate. It is particularly with liquids of relatively high solids content that this surface layer forms and clogs the membrane pores very quickly, retention reaching levels of around 100% after only a short time, so that the membrane becomes impermeable to the materials. In order to make the membranes repermeable to the materials, the basically continuous process has to be interrupted for cleaning to be carried out.
Of particular interest may be U.S. Pat. No. 4,420,398-Castino, which describes the crossflow ultrafiltration of cell-produced biological by-products having molecular weights of including 15,000 to 70,000 daltons. Crossflow filtration is also described in U.S. Pat. Nos. 4,191,182-Popovich, et al., and 4,212,742-Solomon, et al.